Abstract

2595

Background: Cyclin E/cdk2 is a G1-S phase regulatory protein and has an established role in many cancers. Cyclin E overexpression is correlated with a poor prognosis in breast cancer patients. The Gynecologic Oncology Group recently reported that cyclin E overexpression is a poor prognostic factor for patients with advanced ovarian cancer. The purpose of this study was to evaluate the presence of cyclin E overexpression in normal endometrium, endometrial hyperplasia, and endometrial cancers (both primary and recurrent cancers). Methods: One hundred and fifty-one specimens were available for analysis. These included: 7 normal endometrium, 5 endometrial hyperplasia, 74 endometrioid endometrial carcinomas (EEC), 23 uterine papillary serous carcinomas (UPSC), 23 mixed malignant mullerian tumors (MMMT), 10 recurrent endometrioid carcinomas (R-EEC), and 8 recurrent uterine papillary serous carcinomas (R-UPSC). Histologic sections of formalin, fixed paraffin embedded specimens were stained with cyclin E monoclonal antibody (Neomarkers, Fremont, CA). Overexpression was considered if greater than 40% of the specimens had moderate (2+) to heavy (3+) nuclear staining. All slides were evaluated with a gynecologic pathologist. Results: Overexpression of cyclin E was not demonstrated in normal endometrium (0/7) or endometrial hyperplasia (0/5). Of the EECs, 20/74 (27%) overexpressed cyclin E. This varied by grade [grade 1: 2/15 (13%); grade 2: 3/23 (13%); grade 3: 15/31 (48%); grade 1&2 vs grade 3, p=0.001]. Of the UPSCs, 14/23 (61%) overexpressed cyclin E. 57% (13/23) of the MMMTs expressed cyclin E. Within the MMMTs, cyclin E overexpression was localized in the carcinoma component in 7 of 13 cases, in the sarcoma component in 4 of 13 cases, and in both the carcinoma and sarcoma components in 2 cases. There was a significant difference in overexpression between the EECs and the UPSCS (p=0.009) and MMMTs (p=0.026). There was no significant difference between the high grade EECs (grade 3), UPSCs, and MMMTs. 30% (3/10) of R-EECs and 100% (8/8) of R-UPSCs overexpressed cyclin E (p=0.004). Conclusions: Endometrial cancer cells overexpress cyclin E, and overexpression of cyclin E is associated with progression of endometrial cancer tumor grade. Cyclin E overexpression is not found in benign endometrial tissue. High grade EECs have more cyclin E overexpression than lower grade tumors. Cyclin E overexpression is common in high risk histologic subtypes, poorly differentiated EECs, and recurrent endometrial cancers. These findings suggest that cyclin E overexpression may be an indicator of endometrial cancer progression and possibly play a role in endometrial pathogenesis.